ABSTRACT
As part of a development program to offer alternatives to chlorofluorocarbon (CFC) containing metered-dose inhalers, beclomethasone dipropionate has been formulated in a CFC-free system at three strengths: 50, 100, and 200 micrograms/actuation ex valve. To measure serum levels and dose proportionality of the beclomethasone derived from beclomethasone dipropionate, 13 mild to moderate asthmatic patients received a single dose of eight inhalations from each strength according to a double-blind crossover design. Seven patients were studied over 4 h and six patients over 12 h. For the total doses of 400, 800, and 1600 micrograms studied over 12 h, Cmax and AUC increased in a ratio of 1:1.8:3.1. A good correlation was seen between the fine-particle mass delivered and the in vivo performance of the three strengths. From a clinical point of view, the predictable increases in serum levels with an increase in dose will permit the clinician to effectively titrate a patient with this product.
Subject(s)
Anti-Asthmatic Agents/pharmacokinetics , Anti-Inflammatory Agents/pharmacokinetics , Beclomethasone/pharmacokinetics , Nebulizers and Vaporizers/standards , Administration, Inhalation , Adult , Anti-Asthmatic Agents/administration & dosage , Anti-Inflammatory Agents/administration & dosage , Area Under Curve , Asthma/blood , Asthma/drug therapy , Beclomethasone/administration & dosage , Beclomethasone/blood , Chlorofluorocarbons , Cross-Over Studies , Dose-Response Relationship, Drug , Double-Blind Method , Female , Half-Life , Humans , Male , Middle AgedSubject(s)
Brain/metabolism , Colchicine/metabolism , Growth , Nerve Tissue Proteins/metabolism , Organoids/metabolism , Animals , Brain/cytology , Brain Chemistry , Brain Stem/metabolism , Cerebellum/metabolism , Cerebral Cortex/metabolism , Dendrites , Female , Hypothalamus/metabolism , Male , Microtubules/metabolism , Nerve Tissue Proteins/analysis , Neuroglia/cytology , Protein Binding , Rabbits , Thalamus/metabolism , TritiumABSTRACT
The possibility was considered that the sleep-like state seen after injection of short chain fatty acids salts into animals is a result of inhibition of the sodium-potassium activated ATPase. Tris salts of short chain fatty acids inhibited brain Na-K ATPase activity in vitro at concentrations similar to intravenous levels causing narcosis in vivo. The inhibition depended on the logarithm of the concentration of a given acid. The concentration of acid anion which caused 50 per cent inhibition of the enzyme system (I50) was determined for straight and branched chain acids with 4-12 carbon atoms per molecule. The log of I50 concentrations plotted against the number of carbon atoms in the molecule gave a straight line; the inhibitory capacity of an acid increased by a factor of 2.3 for each--CH2--added to the carbon chain. It is suggested that both fatty acid narcosis and the enzyme inhibition result from fatty acid molecules forming an ordered array along the membrane in association with membrane lipids.